Tumor relapse remains the major cause of failure in patients transplanted for advanced stage hematopoietic malignancies. A better understanding of the cellular and molecular basis of tumor recognition by the immune system may lead to the development of new approaches to overcome this problem. This program includes several novel means to maintain tumor surveillance while minimizing graft-versus-host disease. These are: (1) anti-idiotype vaccination (Project VI), and (2) stem cell isolation (Project IV). It is likely that each of these approaches will give rise to a different, and perhaps unexpected, effector immune response. Monitoring this response and defining the molecular basis of tumor antigen (immunoglobulin) recognition by cytotoxic T lymphocytes are the aims of this proposal. Although our long term goal is to monitor the T cell immune response for each of the approaches described above, our present aims are directed at monitoring and characterizing the immune response to idiotype vaccination. Specifically, we propose to: (1) monitor humoral and cellular anti-idiotype response before and after idiotype immunization and correlate this with clinical course and outcome, (2) generate and characterize idiotype specific T cell lines, and (3) define the molecular form(s) in which idiotype specific T lymphocytes recognize immunoglobulin. These studies may help define new antigen specific diagnostic reagents and therapeutic approaches. Such highly specific approaches are clearly feasible and their applications transcend the B cell lymphomas.